Book Review

Molecular Mechanisms of Cardiac Hypertrophy and Failure

N Engl J Med 2006; 355:2795-2796December 28, 2006

Article

Molecular Mechanisms of Cardiac Hypertrophy and Failure
Edited by Richard A. Walsh. 736 pp., illustrated. Abingdon, England, Informa Healthcare/Taylor & Francis, 2005. $749.95. ISBN: 1-84214-248-8

Twenty years ago, the American Heart Association sponsored a symposium in Boston that constituted the first national meeting focused exclusively on the molecular biology of cardiovascular disease. Other disciplines of medicine had already moved into the molecular era, but this meeting represented a major shift for the field of cardiovascular research. Increasingly, investigators were taking advantage of the new tools afforded them by discoveries in molecular biology to answer important questions about the molecular and cellular mechanisms responsible for the development of cardiovascular disease. In the ensuing 20 years, the development of new technology and its linkage with traditional biochemical and physiological assessments have led directly to an information explosion and indirectly to a diverse group of new treatments and diagnostic tests for patients with cardiovascular disease.

Although advances have occurred in all areas of cardiovascular research, a remarkable amount of new information has emerged concerning cardiac hypertrophy and failure, pathologic processes that affect more patients in the United States than any other disease. Molecular studies have identified the mutations responsible for the lethal arrhythmias in patients with the Brugada syndrome, the skeletal- and cardiac-muscle abnormalities in patients with muscular dystrophy, and the monogenic causes of hypertrophic cardiomyopathy. In addition, transgenic mouse models have supplied the theoretical underpinning for the use of beta-blockers and angiotensin-receptor blockers in the treatment of heart failure.

In an elegant new book, editor Richard Walsh and his associate editors and contributors have detailed the major advances over the past two decades in our understanding of the molecular pathobiology of cardiac hypertrophy and heart failure. By dividing the book into four sections — each representing a major component of heart-muscle disease (hypertrophy, contractile dysfunction or failure, arrhythmias, and genetics) — Walsh has created a structure that allows readers to focus on a particular element or area. In addition, the initial chapters in each of the four sections are concise yet descriptive overviews of the relevant pathobiology and epidemiology, thus providing an intellectual platform for the student or young investigator seeking to develop an understanding of the field. For example, the first section, “Mechanisms for Cardiac Hypertrophy,” begins with chapters on the mechanisms of normal cardiovascular growth and development, cell-cycle control in cardiomyocytes, and molecular mechanisms of cardiac myocyte death. These introductory chapters set the stage for later discussions on the role of transcription factors, the extracellular matrix, altered signal transduction, and oxidative stress in the development of pathologic or physiologic hypertrophy. Similarly, the section on arrhythmogenesis begins with a well-illustrated and clearly written chapter on the cellular and molecular bases of excitation in normal cardiac tissue. This introductory chapter provides the fundamental information necessary for understanding later chapters on abnormalities in ion currents and repolarization in the failing heart, new therapeutic targets for arrhythmia prevention, and genetic factors underlying inherited electrophysiological abnormalities.

For both the student and the established clinician or investigator, a strength of this work is that each section was edited by one or more associate editors who are leading authorities in the field: Michael Schneider, Stephen Vatner, Eduardo Marban, and Jon Seidman and Christine Seidman. Furthermore, the chapters were written by investigators of great stature who have made seminal contributions to the fields that they discuss. Each chapter provides a comprehensive overview of the field as well as up-to-date information. It is also important to note that in contrast with many multiauthored books, there is a consistency in the presentation of the figures and tables and a uniformity and flow in the text that make this book very readable. A substantial number of useful and informative color plates add to the richness of the book. Although these plates are collected at the beginning of the book, the black-and-white figures that appear throughout the body of the text are clearly annotated to remind the reader to refer to the color plates.

At a time when our understanding of the molecular and cellular biology of heart-muscle disease is expanding exponentially, this well-written multiauthored book aptly summarizes a wide range of information in a readable and instructive manner. It should be a valuable resource for a diverse group, including students, residents, and fellows who are just beginning their journey into the world of cardiovascular research as well as clinicians who want to understand the scientific underpinning of new therapeutic or diagnostic tools. Indeed, even the established investigator will find this to be an important book to have on the shelf as a ready reference for answering the occasional question or as a textbook for teaching students or residents.

Arthur M. Feldman, M.D., Ph.D.
Jefferson Medical College, Philadelphia, PA 19107
arthur.feldman@jefferson.edu